Stimulation of aldose reductase activity by tubulin: effect of phenolic acid derivatives

RIVELLI JF; OCHOA AL; SANTANDER V.; ARCE C; CASALE C. H.

cordoba

Congreso; saib 2016; 2016

The main pathogenic pathwayof diabetes is activation of the enzyme aldose reductase (AR). In ourlaboratory we describe a new regulatory mechanism of AR activity by tubulininteraction. The tubulin increased 7 times the AR activity. This activationinduces changes in microtubule dynamics and inhibition of Na+,K+-ATPase.We also demonstrate that 3-nitro-L-tyrosine (3-NTyr) and tyrosine (Tyr) are able to prevent tubulin/AR association and, in a model ofdiabetic rats, the administration of 3-NTyr prevents the development ofdiabetic cataracts. The most importantfamily of inhibitor compounds of AR is the carboxylic acids. Althoughstructurally Tyr and 3-NTyr are different they share two characteristics: thepresence of an aromatic ring and a carboxylic substituent. The objective of the present study was evaluatedifferent phenolic acid derivatives in their ability to prevent the formation of tubulin/ARcomplex and enzyme activation. The drugs tested were: 3-hidroxy-4-methoxymandelic acid, 4-Hidroxy-3-Methoxy Phenylacetic acid, 3,4-Dihidroxyphenylacetycacid, DL-4-Hydroxy-3-methoxymandelicacid, â-4-hydroxy-3-methoxyphenyl lactic acid, Vanilic acid, 3,4- dihydroxyphenyl alanine. All drugstested showed you were able to prevent tubulin/AR complexformation, enzyme activation and tubulin polymerization in cells cultured inhigh glucose. These results allow us to propose toderivatives phenolic acids as regulators of AR activity and preventers possibleof the formation of diabetic cataract.